Modular Trial of sEphB4-HSA in EphrinB2-High Solid Tumors
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorVasgene Therapeutics, Inc
About this trial
Patients with solid tumors that have high expression levels of EphrinB2 are treated with regimens that include EphrinB2 inhibitor, sEphB4-HSA. The primary objective of this study is to demonstrate additive therapeutic benefit for sEphB4-HSA. The secondary objectives are to determine whether the sEphB4-HSA containing regimen is safe and whether the oncological endpoints of importance in each cohort improve as a result of treatment with sEphB4-HSA containing regimen relative to a predefined threshold or to a control arm in the cohort where available. Treatment continues until progression of disease or unacceptable toxicities arise.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Willing and able to provide informed consent.
Men and women 18 years of age, or older.
Must provide the cell block or a minimum of 15 slides from the diagnostic biopsy or archival tissue.
Tumor tissue must be submitted for molecular profile through a commercial service such as Tempus, CARIS, Foundation One, etc. This must include a PD-L1 assay.
Disqualifiers
Patients with known symptomatic brain metastases requiring systemic corticosteroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable. Mild neurological deficit is allowed, if it does not interfere with the ability to judge the safety on the trial.
History of or active autoimmune disorders (including but not limited to: Crohn's Disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Grave's disease) and other conditions that compromise or impair the immune system.
Known active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) -related illness. Routine testing is not required; however, treating physicians may use their discretion to determine whether testing is necessary.
Uncontrolled adrenal insufficiency.
Trial design
Design model
Parallel
Treatments tested in this trial
SEphB4-HSA
DrugA recombinant protein comprised of the soluble form of human receptor EphB4 fused to human serum albumin.
Pembrolizumab
DrugAntibody to human PD-1.
Gemcitabine
DrugA chemotherapy drug used to treat various types of cancer.
Cisplatin
DrugA type of chemotherapy drug called an alkylating agent used to treat various types of cancer.
Enfortumab vedotin
DrugNectin-4-directed antibody and microtubule inhibitor conjugate.
Treatment groups
700 Participants
are divided into 4 treatment groupsGroup A: sEphB4-HSA + Pembrolizumab in MIBCExperimental treatment 2 interventions
Group B: Gemcitabine-Cisplatin (GC) or Pembrolizumab Alone in MIBCActive comparator 3 interventions
Group C: sEphB4-HSA + Pembrolizumab in Naive mUCExperimental treatment 2 interventions
Group D: Enfortumab Vedotin (EV) + Pembrolizumab in Naive mUCActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
Improved pathological response (pCR) in sEphB4-HSA+Pembro vs. Standard of Care for MIBC
Pathologic complete response (pCR), a binary outcome. pCR is defined as absence of the muscle invasive component of the tumor in the radical cystectomy specimen by pathologic review. CIS (pTis), pT1, and pTa are considered to be pCR. All patients with pCR must have pN0/M0. Patients don't have pCR due to refusal of radical cystectomy, dropout prior to radical cystectomry, or pathologic evaluation results are inconclusive or unknown will be classified as non-responders in the ITT.
Time frame
Through study completion, an average of 6 months2
Improved Overall Survival (OS) in sEphB4-HSA+Pembro vs. Standard of Care for MIBC
Overall survival (OS) defined as period from randomization to death from any cause. OS will be censored at the last follow-up if patients are known to be alive. OS is a time to event variable of the primary interest.
Time frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months3
Improved Radiographic Objective Response Rate (ORR) in sEphB4+Pembro vs. Control in mUC
Using RECIST 1.1 on CT or MR imaging of chest, MR imaging of Chest, Abdomen and Pelvis every 6 weeks for the first 3 months and then every 12 weeks.
Time frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months4
Non-inferior Overall Survival (OS) of sEphB4+Pembro vs. Control in mUC
Overall survival (OS) defined as period from randomization to death from any cause. OS will be censored at the last follow-up if patients are known to be alive. OS is a time to event variable of the primary interest.
Time frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 monthsSecondary outcomes
1
Improved Disease Free Survival and/or Event Free Survival in sEphB4 vs. control for MIBC arm.
Event free survival (EFS): defined as time from randomization to any of the following events: documented disease progression precluding surgery, progression or recurrence diasease after surgery, or death due to any cause. Progresssion/recurrence will be assessed per RECIST 1.1. Patients who undego surgery with incomplete resection will be considered to have an event. Patients who start any subsequent anti-cancer therapy without a prior reported progression/recurrence will be censored at the last evaluable tumor assessment prior to initiation of the subsequent anticancer therapy. Patients who remain free of abovementioned events will be censored at the last follow-up time.
Time frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months2
Improved toxicity of EphB4-HSA + Pembro in MIBC vs. control
Toxicity, as measured by the CTCAE v5.0, will be evaluated from start of study treatment to 7 days after the end of the study treatment.
Time frame
From start of study intervention until one week after cessation of study intervention, assessed up to 60 months3
Improved Duration of Response and/or Progression Free Survival in sEphB4 vs. control for mUC arm.
Disease free survival is defined as the time from the date of surgery to the earlier of disease recurrence, or death from any cause. Disease recurrence includes muscle-invasive recurrences specifically in the bladder, metastatic disease outside the bladder, or death. Patients alive without documented disease recurrence will be censored at the date of last disease assessment. Measured using RECIST 1.1 on CT or MR imaging of chestMR imaging of Chest, Abdomen and Pelvis every 6 weeks for the first 3 months and then every 12 weeks.
Time frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months4
Improved toxicity of sEphB4-HSA + Pembro in mUC vs. control
Toxicity, as measured by the CTCAE v5.0, will be evaluated from start of study treatment to 7 days after the end of the study treatment.
Time frame
From start of study intervention until one week after cessation of study intervention, assessed up to 60 monthsSponsors and contacts
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Source ClinicalTrials.gov